Oral presentations Group 3B

Parallel Session 3
Tuesday, June 18, 2024
16:00 - 17:00
Lecture Theatre 3


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Mr Sheveen Wijesuriya
King's College London

Quantifying Infiltration of Macrophages with CD163 Marker in Head & Neck Tumour Microenvironment Post-Radiotherapy

16:00 - 16:15


Head and neck squamous cell cancers (HNSCC) rank as the 6th most common cancer globally, resulting in approximately 300,000 deaths worldwide [1]. Radiotherapy (RT) stands as a prominent treatment modality. Extensive research has been conducted to assess the efficacy of this treatment, aiming to minimise the side effects experienced by patients. Among the factors influencing treatment response, M2 macrophages have emerged as significant contributors, given their pro-tumour and anti-inflammatory characteristics. Consequently, greater infiltration of M2 macrophages within the tumour post-RT could exacerbate resistance to treatment.
This project aims to quantify M2 macrophages, using the macrophage marker CD163, within the entirety of head and neck tumours.
Tumours were generated using the murine head and neck cancer cell line MTCQ1, with separate groups left untreated or subjected to radiation (8 Gy dosage). Tumour collection occurred on days 1, 3, 5, 7, and 10, followed by therapeutic intervention. The creation of the slides involved the fixation of the collected tumours in 4% paraformaldehyde, processing and embedding in paraffin. Utilising ImageJ, the percentage of positively stained CD163 cells was determined across the entire tumour.
On ANOVA analysis, a significant interaction was observed between days and treatment (P=0.0325). In the irradiated group (n=15), there was a progressive 2.87% increase in the percentage of positively stained cells up to day 7. Notably, the interaction between untreated and irradiated tumour groups on day 7 exhibited strong statistical significance (P=0.0027), the irradiated group being 2.54% greater than the untreated group.
The findings suggest potential implications for guiding RT in HNSCCs. Day 7 presented the most notable disparity between untreated and irradiated groups, highlighting a potential window for targeting post-RT resistance and specifying the optimal radiation dosage. However, these preclinical observations warrant replication in clinical trials to validate their relevance for patient care.
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Dr Matthew Watson
Mid And South Essex NHS Trust

Too Much Skin In the Game: A Dermatopathology Audit of Cancer Services at Broomfield Hospital, MSE NHS Trust

16:15 - 16:30



In the East of England there has been an 89% increase in pathology cases clinically labelled as possible cancer between 2018 to 2022 (1). Dermatology is a specialty driving this increase in urgent workload (1). The two week wait (2ww) concept is a pathway for patients with suspected cancer which is focused on providing rapid diagnoses and is outlined under the NHS constitution (2).


To audit the cancer dermatopathology service and identify cases labelled as possible cancer/2ww that could be downgraded to non-urgent.


Laboratory records identified all dermatology cases that arrived in the laboratory in October 2023. Urgency, clinical impression, and histological diagnosis were recorded for each sample. Samples sent as a 2ww were isolated. Cases were graded as appropriate and inappropriate for the 2ww pathway. Appropriate cases included clinically possible melanomas, squamous cell carcinomas and basal cell carcinomas (BCC) in high-risk areas (eyes, lips, nose). Re-excisions were defined as removal of a lesion that had previously been proven to be malignant histologically.


981 patients were processed in the laboratory in October 2023. 634 patients (65%) were reported on the 2ww pathway. Of these 634 2ww patients, 189 (30%) were deemed inappropriate for the 2ww pathway based on clinical impression alone. Re-excisions (67: 35%) and BCCs in low risk areas (25: 13%) made up 92 (48%) patients of this inappropriate cohort of samples on the 2ww pathway. Removing these 92 patients from the initial 634 patients would reduce the 2ww case load by 15%.


Many dermatology samples are inappropriately labelled as a 2ww suspected cancer sample based only on clinical impression. This short abstract does not include final histological diagnoses. Groups of inappropriate samples should be identified and removed from this pathway with an aim to reduce urgent workload.
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Mr Toby Curless

Novel quantitative digital pathology pipeline unveils distinct regional patterns of misfolded protein pathologies in Parkinson’s disease

16:30 - 16:45


Background: The characteristic α-synuclein inclusions in Parkinson’s disease (PD) are variably accompanied with concomitant amyloid-β and tau neurofibrillary tangle pathology, which may influence the rate to dementia progression in PD. However, the extent of misfolded protein pathologies across the brain in PD is not fully described, due to challenges of current semi-quantitative assessment approach. There is therefore a need to establish novel pipelines for consistent and scalable quantification of misfolded protein pathologies.

Purpose: To use machine learning-based tools for quantitative image analysis on digital whole slide images across multiple brain regions to generate automatically quantified data for further downstream integration with clinical phenotypes, genetic profiles and regional transcriptomic signatures for identifying disease subtypes.

Methods: Digitally scanned regional brain sections stained for alpha-synuclein, amyloid-beta and hyperphosphorylated tau from PD and control cases were segmented into regions of interest to quantify the pathology in specific anatomical regions. Using open-source pathology image analysis software (QuPath), algorithms have been developed for large-scale high-throughput quantification of misfolded protein pathology.

Results: We have quantified misfolded protein load across multiple brain regions in over 300 cases. Comparative analyses of these pathologies within the same region and between regions has identified distinct patterns of pathology between different presentations of PD, based on clinical and genetic data.

Conclusion: We report a novel digital pathology pipeline that is reproducible and robust for quantification of misfolded protein pathology in PD. Such approaches can now be developed to include other pathological markers and established for other disease profiles.
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Dr Sinha Tariq
Royal Liverpool University Hospital

EWSR1-SMAD3 positive fibroblastic tumour: a series of three cases.

16:45 - 17:00


EWSR1-SMAD3 fibroblastic tumour is a rare cutaneous soft tissue neoplasm, most commonly arising in acral sites. The tumour has a well-circumscribed, nodular architecture and consists of uniform, bland, fibroblastic spindle cells set within a collagenous to myxoid stroma.
We present three cases of EWSR1-SMAD3 fibroblastic tumour with the aim of elucidating the morphological features and immunoprofile and determine when to consider it in the differential diagnosis and consider further molecular testing.
A search of the electronic record (tertiary soft tissue pathology referral service).
All three cases occurred in the women aged between 20-69, all three occurred on the feet and ranged between 6mm to 10mm in maximum dimension.

Microscopically common features included fascicles of bland spindle cells set in fibrous or fibromyxoid stroma. The cells contained eosinophilic cytoplasm and oval blunt-ended nuclei. Stromal hyalinisation and dystrophic calcification were noted in one case. No atypia, significant mitotic activity or necrosis was present.

All three tumours demonstrated strong diffuse expression of ERG and CD34 negativity.

One tumour showed recurrence after 9 months.

Fluorescence in-situ hybridisation analysis showed an abnormal signal pattern indicating a rearrangement involving the EWSR1 gene and expression of fusion gene EWSR1:SMAD3.

Our series confirms the findings from the literature and further elucidates the histological spectrum. EWSR1-SMAD3 fibroblastic tumour is a little known entity and should be considered in this morphological context combined with ERG positivity and CD34 negativity.
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Dr Yasuhiro Sakai
Associate Professor
Hamamatsu University School of Medicine

Elucidation of lymphocyte dynamics and development of a tumourigenesis model based on the GANP/DSS1 family

17:00 - 17:15


We have (1) studied lymphocyte dynamics, particularly B-cell dynamics, during chronic inflammation in terms of migration and post-migration activation and (2) developed a tumourigenesis model based on GANP/DSS1 (germinal centre-associated nuclear protein, deleted in split hand or split foot) family.
GANP is an essential molecule in lymphocytic post-migration activation during chronic inflammation. It is highly expressed in lymphocytes that migrate to damaged tissues and is closely associated with altered lymphocyte dynamics. GANP is crucial for the affinity maturation of antibodies and maintenance of B-cell properties. For example, when immunising IgH‐ganp transgenic mice with antigens, GANP overexpression markedly expands B-cell receptor diversity, resulting in higher affinity antibodies being produced effectively. When GANP is aberrantly expressed, centroblasts in germinal centres lose their B-cell properties and transdifferentiate into macrophages. Hodgkin lymphoma cells often lose their B-cell properties, such as CD20 positivity, due to frequent abnormal GANP expression.
Additionally, GANP forms a transcription-export-2 (TREX-2) complex with other protein molecules such as DSS1, which plays an important role in mRNA metabolism. When the TREX-2 complex is dysfunctional, an abnormal DNA:RNA hybrid structure known as an “R-loop” is formed, resulting in transcription-coupled DNA damage. Therefore, DNA instability induced by the GANP/DSS1 family may contribute to the affinity maturation of antibodies and post-migration activation in B cells, while also being closely associated with tumourigenesis in nonimmune cells. For example, breast cancers with aberrant GANP or DSS1 expression are insensitive to DNA synthesis inhibitors and have a poor prognosis. Furthermore, GANP is associated with testicular teratomagenesis because human postpubertal-type teratomas overexpress GANP, and midline teratomas can be artificially produced in the female uterus and male testes of ganp transgenic mice. In conclusion, tumourigenesis and teratomagenesis models were effectively developed by studying lymphocyte dynamics in areas beyond immunology.


Graeme Murray
The Pathological Society