Pleomorphic Adenoma of Neck: Case Report

Pleomorphic adenomas are benign tumour of the salivary glands that mostly affect the parotid gland. The tumor's "pleomorphic" form can be explained by its epithelial and connective tissue origins. Females between the ages of 30 and 50 are more likely to get the tumour. The tumour usually presents as asymptomatic swelling that progresses slowly. The majority of treatment is surgical removal of the tumour mass, with special attention paid to preserving the facial nerve. This is a case report of a 42-year-old female patient who had a pleomorphic adenoma of the submandibular gland. On the right side of the face, the patient had a slowly growing asymptomatic swelling. Pleomorphic adenoma is the commonest salivary gland tumor characterized by diverse histomorphological features. Early diagnosis and treatment plan entails thorough history taking, clinical examination, coupled with radiographic and histopathological findings.

Bioengineering the ameloblastoma tumour to study its effect on bone nodule formation

Ameloblastoma is a benign, epithelial cancer of the jawbone, which causes bone resorption and disfigurement to patients affected. The interaction of ameloblastoma with its tumour stroma drives invasion and progression. We used stiff collagen matrices to engineer active bone forming stroma, to probe the interaction of ameloblastoma with its native tumour bone microenvironment. This bone-stroma was assessed by nano-CT, transmission electron microscopy (TEM), Raman spectroscopy and gene analysis. Furthermore, we investigated gene correlation between bone forming 3D bone stroma and ameloblastoma introduced 3D bone stroma. Ameloblastoma cells increased expression of MMP-2 and -9 and RANK temporally in 3D compared to 2D. Our 3D biomimetic model formed bone nodules of an average surface area of 0.1 mm2 and average height of 92.37 $$\pm $$ ± 7.96 μm over 21 days. We demonstrate a woven bone phenotype with distinct mineral and matrix components and increased expression of bone formation genes in our engineered bone. Introducing ameloblastoma to the bone stroma, completely inhibited bone formation, in a spatially specific manner. Multivariate gene analysis showed that ameloblastoma cells downregulate bone formation genes such as RUNX2. Through the development of a comprehensive bone stroma, we show that an ameloblastoma tumour mass prevents osteoblasts from forming new bone nodules and severely restricted the growth of existing bone nodules. We have identified potential pathways for this inhibition. More critically, we present novel findings on the interaction of stromal osteoblasts with ameloblastoma.

Effect of Cold Atmospheric Plasma on Epigenetic Changes, DNA Damage, and Possibilities for Its Use in Synergistic Cancer Therapy

Cold atmospheric plasma has great potential for use in modern medicine. It has been used in the clinical treatment of skin diseases and chronic wounds, and in laboratory settings it has shown effects on selective decrease in tumour-cell viability, reduced tumour mass in animal models and stem-cell proliferation. Many researchers are currently focusing on its application to internal structures and the use of plasma-activated liquids in tolerated and effective human treatment. There has also been analysis of plasma’s beneficial synergy with standard pharmaceuticals to enhance their effect. Cold atmospheric plasma triggers various responses in tumour cells, and this can result in epigenetic changes in both DNA methylation levels and histone modification. The expression and activity of non-coding RNAs with their many important cell regulatory functions can also be altered by cold atmospheric plasma action. Finally, there is ongoing debate whether plasma-produced radicals can directly affect DNA damage in the nucleus or only initiate apoptosis or other forms of cell death. This article therefore summarises accepted knowledge of cold atmospheric plasma’s influence on epigenetic changes, the expression and activity of non-coding RNAs, and DNA damage and its effect in synergistic treatment with routinely used pharmaceuticals.

STEM-18. STROMAL EXTRACELLULAR VESICLES DRIVE GLIOMA STEM CELL REPROGRAMMING

Glioblastoma multiforme (GBM) represents the most frequent and lethal form of brain tumors originating from glioma stem cells (GSCs). GBM remains lethal because the rate limiting patho-mechanisms remain poorly understood. In this regard, few limitations involve the diversity 'between' cellular states and the molecular/cellular complexity 'within' the tumour mass. Using cell based- and mouse- models, we explored extracellular vesicle (EV) mediated interactions between cancer and stromal cells impacting phenotypes of GSCs as a function of their molecular subtype. EVs are spherical membrane structures that cells release to expel different molecular cargo (lipids, proteins, RNA, DNA), which can be transported across a distance in the brain and taken up by various ‘recipient’ cells resulting in reprogramming of the recipient cell's content and function. In vivo, GSCs altered their pattern of NOTCH signalling and molecular phenotype as a function of proximity to non-transformed host cells in the brain. In vitro stromal EVs altered GSC sphere forming capacity, proteome and expression of mesenchymal markers. Thus, EV mediated tumour-stromal interactions could represent a biological switch and a novel targeting point in the biology of GBM.

PD-L1 Expression on Circulating Tumour-Derived Microvesicles as a Complementary Tool for Stratification of High-Grade Serous Ovarian Cancer Patients

Background: Ovarian cancer (OC) has recently attracted attention for the use of PD-1/PD-L1 axis blocking agents, with durable activity reported only in a subset of patients. The most used biomarker for sensitivity to the PD-1/PD-L1 axis blockade is tumour PD-L1 status by immunohistochemistry. However, patient stratification using this method suffers from intrinsic heterogeneity of OC, likely contributing to the unsatisfactory results obtained so far. Cells communicate with each other by releasing microvesicles (MVs) that carry parental cell surface features. Thus, we hypothesised that PD-L1+ tumour cells (TC) and infiltrating PD-L1+ leukocytes should shed MVs carrying surface PD-L1 that may serve as a proxy for the whole tumour PD-L1 status. Results: We showed for the first time the presence of measurable amounts of TC- and leukocyte-derived PD-L1+ MVs (range: 1.4–178.8 MVs/μL and 6.2–504.8 MVs/μL, respectively) in the plasma of high-grade serous OC (HGSOC) patients (n = 63), using a sensitive flow cytometry platform. The concentration of PD-L1+ MVs of either origin did not associate with the PD-L1 status of TCs and leukocytes in the tumour biopsies, suggesting that the circulating PD-L1+ MVs also included ones from locations not selected for immunohistochemistry analysis and represented the PD-L1 status of the whole tumour mass. In this study, we also describe the serendipitous discovery of circulating PD-L1+ MVs of platelet origin (10.3–2409.6 MVs/μL). Conclusions: The enumeration of circulating PD-L1+ MVs in HGSOC patients may provide a novel direction for assessing the tumour PD-L1 status and contribute to HGSOC patient stratification for immunotherapy interventions. The presence of circulating PD-L1+ MVs of platelet origin, a finding not yet reported in HGSOC patients, warrants further studies.

miRNAs as modulators of cholesterol in breast cancer stem cells: an approach to overcome drug resistance in cancer

: It has been postulated that a small number of cancer stem cells (CSCs) buried in tumour mass drive cancer growth and impart cancer drug resistance. However, their eradication has not been achieved so far as the mechanistic understanding around CSCs’ role in cancer development and growth is limited. The cholesterol accumulation and efflux processes have been shown to play an important role in maintaining cell’s integrity and its sensitivity towards drugs, as altered cholesterol pathways contribute to cancer drug resistance. Emerging evidences have indicated miRNAs as regulators of CSCs, and also as regulators of cholesterol pathways in cancer cells, but a link between the two has not been fully established so far. In this review, we have collated key signalling pathways, and published evidences emphasising the involvement of miRNAs and cholesterol in CSCs related drug resistance. Additionally, we have used bioinformatics analysis to identify miRNAs that may modulate cholesterol pathways in CSCs at molecular level to contribute to cancer drug resistance. Our results that two miRNAs (hsa-miR-34a-5p and hsa-miR-373-3p) interact, and bind to two known Breast CSC markers (CD44 and CD24), and mediate expression of several cholesterol-related genes (INSIG2, APOL2, CYP51A1, HDLB, and DHCR7). Furthermore, survival analysis of the breast cancer patients’ gene expression data revealed that higher expression of these genes is associated with poor disease free survival. We therefore propose that targeting these two miRNAs could possibly provide a way to alter cell’s response to drugs via modulating cholesterol pathway in CSCs.

Selection of headache cases for expedited scanning to assist prompt diagnosis of brain tumour

Aims Patients with brain tumours and headache commonly have poorer cognitive skills, either overtly or covertly, when cognitively tested. Cognitive changes reflect, tumour mass, fronto-temporal location or hydrocephalus, Previous work has demonstrated that the “semantic Verbal Fluency Test (SVFT) -“How many animals can you think of in a minute?” is a useful fast screening test for cognitive issues. Median SVFT in patients with brain tumour on admission is 10 animals. Most GPs can now order “direct access cerebral imaging (DACI)” in patients with headache suspicious of cancer. The waiting times for scanning can be many weeks. The aim of this study was to determine whether low SVFT scores: might be useful to help stratify or expedite DACI. We present data from referrals through and electronic Protocol Based Referral (PBR) pathway for CT scanning over 3 years, to determine whether SVFT might be a useful adjunct to history and examination. Method From 2017, in Edinburgh/Lothians, Scotland, an electronic PBR was developed with involvement of Primary Care Cancer Lead, PBR lead, Neurology, Neurosurgery and Neuro-Imaging for outpatient imaging of patients in the community with Headache Suspicious of Cancer, to expedite their scans. The PBR sat alongside the routine outpatient DACI system. If the forms were correctly filled in Neuro-Radiology prioritised their appointments. The referrer (GP) was asked to complete the ePBR form and SVFT at the time of referral. Other data were also gathered, including: Past Medical History of cancer; other symptoms/signs; and co-morbid conditions and medications filled automatically from the GP system. This formed the dataset. We also retrospectively assessed a) whether English was first language b) past history of Pain Clinic Attendance or Functional Illness and subsequent final diagnosis of headache/condition, through evaluation of electronic GP referral letters through SCI Gateway system of those cases where SVFT was recorded. Results Between March 2017 - November 2019, 669 scans through PBR pathway. (62% females; Mean age 53 years: 60% cases <60 years). SVFT was completed in only 381/669 (57%). Median SVFT was 17. Eleven of 381 cases had cancer (2.9%). 10 cases with cancer had SVFT <17 animals (median 10) (5.32%). One case had SVFT >=17 (35 animals) (0.5%) - CT scan showed small multiple intra-cerebral calcified and non-calcified lesions, consistent with metastases. 12% with PMH cancer had a tumour. Other possible reasons for low SVFT were: co-existing presumed dementia/mild cognitive impairment (19); non native English speakers (12); headache after traumatic brain injury (5); significant small vessel disease/vascular(5); intracranial cysts (4)(pineal / arachnoid, Giant Cell Arteritis (4) (all new - symptomatic); Chiari 1 malformations (2), PMH – encephalitis (1). Interestingly, there were 53 cases with known psychiatric/pain conditions on drugs (e.g. codeine/antidepressants/antipsychotics) with SVFT < 17 words/min. Conclusion People with Headache "Suspicious of Cancer" + SVFT <17 words in a minute are more likely to have a tumour (5.32% vs 0.5%) or other secondary cause for poor cognition. Other probable causes /associations, with SVFT <17 are age, poor English skills, co-existing dementia. SVFT score may be a useful adjunct or “red flag,” to consider, to expedite DACI scan in patients with “Headache Suspicious of Cancer”. A SVFT >=17 in those with Headache Suspicious of Cancer, does not exclude the possibility of an intracranial tumour. Excluding cases with recognised causes for low SVFT e.g. dementia and those with existing chronic pain/psychiatric disease further increases the likelihood of a secondary cause for headache. SVFT should be tested in the persons native language. A larger prospective study is required to establish whether these pilot study data and to examine whether chronic pain, functional neurology are negative predictive factors for secondary headache.

Histopathological study of canine hepatoid gland tumours

Hepatoid gland neoplasms arise due to disorganized and uncontrolled proliferation of cells of hepatoid glands. These are the modified sebaceous glands located mainly in the perianal area. Gross and histological findings of canine hepatoid gland tumours were evaluated. Dogs of different breed, age and sex that were presented to Department of Veterinary Surgery and Radiology, College of Veterinary and Animal Sciences, Mannuthy formed the materials for the present study. Grossly, tumours were solitary or multiple irregular shaped intradermal masses. The excisional biopsy samples were collected in 10 per cent neutral buffered formalin after surgical removal of tumour mass. Histopathologically, the masses were encircled by fibrovascular capsule which extended to the parenchyma as tumour stroma, which separated it into lobules. Two cases of hepatoid gland adenoma one case of hepatoid gland epithelioma and two cases of carcinoma were recognised on histopathological examination. Hepatoid adenoma were characterised by proliferation of hepatocyte like hepatoid gland epithelial cells with extensive sebaceous differentiation and were arranged in cords and anastomosing trabeculae. In hepatoid gland epithelioma, many of the cells were basaloid reserve cells with fewer hepatocyte like cells. Histopathological examination of carcinoma revealed irregular arrangement of the hepatoid cells which showed varying degrees of maturation and marked nuclear pleomorphism. The malignant hepatoid cells had abundant eosinophilic cytoplasm and large nuclei with several prominent nucleoli and mitotic figures.

Vitreoretinal Surgery in the Prevention and Treatment of Toxic Tumour Syndrome in Uveal Melanoma: A Systematic Review

Toxic tumour syndrome (TTS) is a particularly aggressive form of secondary vasculopathy occurring after radiation therapy of uveal melanoma due to the persistence of the necrotic tumour mass inside the eye. The development of TTS confers a particularly unfavourable functional and anatomical ocular prognosis, ultimately requiring enucleation in most cases if untreated. Vitreoretinal (VR) surgery has been successfully applied for treatment and prevention of TTS using both resecting and non-resecting techniques. In this systematic review, we aim to define characteristics of uveal melanomas benefiting the most from secondary VR surgery and to outline the optimal type and timing of VR intervention in such cases. Analysis of the literature reveals that endoresection should be performed within 3 months after radiotherapy to tumours thicker than 7 mm and with a largest basal diameter between 8 mm and 15 mm with post-equatorial location, especially after proton beam treatment. Alternatively, endodrainage remains a valid therapeutic option in eyes with macula-off retinal detachment, tumour diameter larger than 15 mm or ciliary body involvement. VR surgery can be successful in the management of TTS following radiotherapy for uveal melanoma when timing and indication are appropriately evaluated.

571 Case of A Rare Presentation of Solitary Fibrous Tumour of the Pleura (SFTP)

Presentation A 69-year-old male presented with rapidly worsening symptoms of breathlessness, productive cough, and weight loss. Examination revealed a deviated trachea, and no breath sounds on auscultation of the left side of the chest. Investigations Chest X-ray revealed a giant mass associated with a large pleural effusion, subtotal lung collapse and mediastinal shift. FEV1 was 39% predicted and DLCO 62% predicted. Management Due to the severity of presentation, urgent pleural inspection, drainage, and biopsy were carried out. Compression of the heart resulting in tamponade with increased heartrate and breathlessness was suspected Further investigations and management Pleural biopsies and pleural fluid cytology were negative for malignancy. PET-CT showed mild avidity. Definitive management was tumour mass resection via left double space open thoracotomy. Macroscopy/Microscopy/Immunohistopathology Intra-operatively, the tumour was giant, occupying three quarters of the chest cavity. It measured 21 × 14×8 cm. The whole lung was attached to the chest wall with adhesions. Microscopy revealed patternless architecture, high vascularity, hypercellularity, necrosis, elongated nuclei, pale cytoplasms and mitotic activity of 2-3 mitotic figures per 10-highpower-fields. Immunohistochemistry stained positive with CD34, BCL2, CD99, Ki-67 and STAT6. Diagnosis of SFT was suspected; malignant potential could not be predicted. Follow-up was with repeat CT scans for five years. Recurrence risk was given as 20%. Learning points